The peritoneal cavity may be affected by a number of related epithelial cancers. Such cancers are often caused by cancer stem cells (CSCs), which originate somewhere in the peritoneal cavity, including the peritoneum and the fallopian tubes, but may spread to other local organs. CSCs may be responsible for epithelial ovarian cancer, epithelial fallopian cancer, peritoneal cancer, and a wide array of carcinomas that may affect certain organs, such as the lungs, brain, breast, prostate and bowels.
Epithelial ovarian cancer is the most lethal of all gynecologic malignancies and the fourth leading cause of overall cancer deaths in women with a dismal 5-year survival rate of 45.9%. Current standard of care consists of surgical debulking and adjuvant chemotherapy with platinum and taxane, to which more than 80% of patients respond. Unfortunately, the majority of these patients eventually exhibit relapse, and upon disease recurrence the value of the standard of care is limited by the presentation of carcinomatosis and chemoresistance. As such, the majority of patients with recurrent ovarian cancer eventually succumb to the disease.
Minimal advancement in the treatment of recurrent ovarian cancer has been made in the past decade. Evidence in the literature supports the concept that tumors are complex heterogeneous organ-like systems with a hierarchical cellular organization, rather than simply as collections of homogeneous single lineage tumor cells. Ovarian tumors are heterogeneous, and inherently chemoresistant CSCs that are not removed by surgery and survive first-line chemotherapy are able to recreate the tumor and cause disease recurrence. Within the heterogeneous tumor, CD44+ ovarian cancer cells represent the chemoresistant phenotype and particularly, that the CD44+/MyD88+ ovarian cancer stem cell (OCSC) population represents the cancer cell type that can repair and rebuild the tumor. A shift in therapeutic strategy that leads to the development of unique targeted agents that attack OCSCs may enhance cancer care and prolong the survival of many patients.
There is a need in the art for methods of treating epithelial cancers, including ovarian epithelial cancer. Such methods should circumvent the chemoresistance of CSC populations after chemotherapy treatments. There is also a need in the art for methods of treating epithelial cancers, including ovarian epithelial cancer, that prevent or delay recurrence of the cancer. The present invention addresses these needs.